Androgen Society Position Paper on Cardiovascular Risk With Testosterone Therapy.

The TRAVERSE trial found no increased risk of major adverse cardiovascular events (MACE) in men receiving testosterone therapy compared with placebo.

• TRAVERSE enrolled 5246 men at high risk for MACE based on existing heart disease or multiple risk factors.
• Participants were randomized to daily testosterone gel or placebo gel.
• Mean follow-up was 33 months.
• MACE was defined as myocardial infarction, stroke, or cardiovascular death.
• No greater risk of venothrombotic events was observed in men who received TTh compared with placebo.

Two observational studies published in 2013-2014 reported increased cardiovascular risks with testosterone therapy and led to regulatory action.

• The two studies received wide media attention.
• Despite strong criticism of those two studies, the FDA added a cardiovascular warning to testosterone product labels in 2015.
• The FDA required pharmaceutical companies to perform a cardiovascular safety study, which became the TRAVERSE trial.
• The position paper characterizes these studies as having received 'strong criticism.'

Review of prior literature reveals near uniformity of studies reporting no increased MACE with testosterone therapy.

• The supporting literature includes 2 additional large randomized controlled trials.
• Multiple smaller randomized controlled trials also reported no increased MACE.
• Several large observational studies were consistent with no increased cardiovascular risk.
• 19 meta-analyses were identified supporting no increased MACE with TTh.

The Androgen Society took the position that testosterone therapy is not associated with increased risks of heart attack, stroke, or cardiovascular death.

• The society is described as 'an international, multidisciplinary medical organization committed to advancing research and education in the field of testosterone deficiency and testosterone therapy.'
• The position is stated as: 'it has now been conclusively determined that TTh is not associated with increased risks of heart attack, stroke, or CV death.'
• This position was written in direct response to the publication of TRAVERSE results in June 2023.
• The position encompasses findings from TRAVERSE combined with the broader prior literature.